We will apply clinically our discovery that Thomsen-Friedenreich (T) antigen is carcinoma-associated. Human breast, colon, stomach, and lung carcinoma patients show cell-mediated as well as humoral immune responses in vivo and in vitro towards T antigens. As far as studied these observations hold also for Tn antigen. T antigen does not occur in reactive form in healthy humans; it is always masked by neuraminic acid. T antigen is readily prepared by chemical methods from isolated human red cell MN antigens in chemically and physically well-defined and innocuous form. So far, all patients with invasive breast carcinoma showed a delayed recall hypersensitivity reaction upon i.d. injection of T antigen but none of the healthy controls did. Our results have been confirmed at the Sloan-Kettering Institute. We want to expand our in vitro and in vivo studies on the value of human (breast) carcinoma-associated blood group MN precursor T antigen in immunodiagnosis, monitoring and screening tests. We want to study diagnostically patients suspected of having breast carcinoma and additional control groups and patients suspected of having other carcinoma. We will include patients with a variety of infections and chronic debilitating diseases. We will modify T antigen and also make it less hydrosoluble to enhance cell-mediated immune responses against it. This may increase the value of diagnostic tests and therapy. We have been treating 8 breast carcinoma patients (Stages II - IV) and one Stage I patient with T antigen for up to 45 months (as of January 1978). Because of encouraging preliminary results we want to expand the number of patients on this immunotherapy. Adjuvant immunotherapy with T antigen and autochthonous neuraminidase-treated cancer cell membranes will be given to Stages II-IV patients. Since Stage I breast carcinoma patients possess immune reactivity against T antigen, we plan to use it as the sole therapeutic agent in such patients. We will do in vivo and in vitro tests to monitor the disease, to assess success or failure of therapy. T antigen may have preventive possibilities.